A Chemical Model of Catechol-O-methyltransferase : Methylation of 3, 4-Dihydroxybenzaldehyde in Aqueous Solution

Abstract

The reaction of 3, 4-dihydroxybenzaldehyde (LH₂) and dimethylsulfate (DMS) to form the m-and p-O-methylated products (vanillin and isovanillin, respectively) in aqueous 2-(N-morpholino)ethane sulfonate buffer was studied kinetically. The products were determined by means of high-performance liquid chromatography. The O-methylation occurred principally at the p-hydroxyl group in the absence of divalent metal ions. In the presence of Cu(II), the m-methylation was promoted and became predominant. Zn(II) showed a similar but less pronounced effect. The effects were explained in terms of the complex formation of LH₂. The second order rate constants for the m-and p-methylation of the species, LH₂, CuL and CuL^2-₂ by DMS were calculated. The values and their ratio for the m-/p-reactions increased in the order of LH₂<CuL<CuL^2-₂. The reaction may serve as a chemical model for catechol-O-methyltransferase, which requires divalent metals and catalyzes the m-methylation.